The objective of this grant is to purchase a triple quadrupole mass spectrometer to replace an existing 10-year old PE-Sciex API III instrument. This instrument will support the research activities of seventeen UAB faculty and six faculty at four other institutions. The advantages of the requested instrument are considerably higher sensitivity (expected at least 20-fold to allow detection of 50 fmole in LC-MS), a more modern computing operating system and software, and a three times higher throughput as a result of switching from a cryogenic pumping system to a turbomolecular one. The triple quadrupole mass spectrometer is requested to provide state-of-the-art quantitative LC-MS analysis using multiple reaction ion monitoring (MRM). It will be applied to analysis of polyphenols and their metabolites in a series of NIH-funded grants at UAB, the Northern California Cancer Center, Baylor College of Medicine, Purdue University, and Wake Forest University. These studies range from those using cell culture, rodent and primate models, to a clinical trial. In one study at UAB, measurement of interstitial fluids will be carried out using a nanoelectrospray ionization source. A similar source will be used to assist a group of UAB investigators who wish to apply methods for the quantitative analysis of proteins. Based on experience with the construction of a specialized nanoelectrospray source we constructed from the Protana interface on the Sciex API 3, as little as 1 fmole should be quantitatively measured using MRM analysis. It is anticipated that a commercial nanospray interface for use in nanoLC-MS analysis will be available by the fall of 2003.